Design, Synthesis, and Biological Evaluation of New Peptide Analogues as Selective COX‐2 Inhibitors

A new class of peptide derivatives possessing SO2Me and N3 pharmacophores at the para position of a phenyl ring bound to different aromatic amino acids were synthesized based on solid‐phase synthesis methodology, and evaluated as selective cyclooxygenase‐2 (COX‐2) inhibitors. One of the analogues, i.e., compound 2a as the representative of this series, was recognized as the highest selective COX‐2 inhibitor with a COX‐2 selectivity index of >500. The structure–activity relationships (SARs) acquired indicated that compound 2a containing a 4‐(methylsulfonyl)benzoyl group as a pharmacophore and tyrosine as a ring bearing amino acid in the second position and glutamic acid as the C‐terminal amino acid can give the essential geometry to provide selective COX‐2 inhibitory activity. Antiproliferative activity of the synthesized peptides (1a–7b) was also determined against four different human cancer cell lines, including MCF‐7, HepG2, A549, and HeLa. According to our results, A549, HepG2, and MCF7 seemed to be more sensitive cell lines than HeLa cells encountering these compounds, which gave inhibitory action with IC50 values from 4.8 to 64.4 µM. In this regard, compounds 3a and 2b displayed the best inhibitory activity against the cell lines. Moreover, a good correlation was observed between the antiproliferative potency and the COX‐2 inhibitory activity of compounds 1a, 2a, 2b, and 5b. Such findings suggest that one of the mechanism of anticancer activity of these peptides may be through the COX‐2 inhibitory action.

A new class of peptide derivatives possessing SO2Me and N3 pharmacophores at the para position of a phenyl ring bound to different aromatic amino acids were synthesized by solid‐phase synthesis methodology and evaluated as selective cyclooxygenase‐2 (COX‐2) inhibitors and anticancer agents. Compounds 3a and 2b displayed the best potency against the studied cancer cell lines. Compounds 1a, 2a, 2b, and 5b showed good correlation between their antiproliferative and COX‐2 inhibitory activity.

Abstract
The single radial immunodiffusion assay has been the accepted method for determining the potency of inactivated influenza vaccines since 1978. The world‐wide adoption of this assay for vaccine standardisation was facilitated through collaborative studies that demonstrated a high ... mehr

Abstract
Background
Whether morbidity from the 1918‐19 influenza pandemic discriminated by socioeconomic status has remained a subject of debate for 100 years. In lack of data to study this issue recent literature have hypothesized that morbidity was “socially neutral”.
Objectives ... mehr